This research is designed to study the behavioral pharmacology of cocaine in humans, characterizing its behaviorally toxic as well as performance enhancing effects and correlating these with its physiological and neurochemical effects. We are proposing to study both the pharmacokinetics of cocaine using three routes of administration, and the interaction of cocaine with alcohol, tobacco, marijuana and diazepam. We will study the drug interactions using a battery of behavioral and physiological measures we have previously demonstrated to be sensitive to cocaine. Our second area of investigation involves the experimental analysis of variables relevant to drug self-administration by humans. We plan to employ a choice procedure using both the intravenous and intranasal routes of administration, and will investigate the effects of various pharmacological and behavioral variables. These include infusion duration, response cost, addition of a non-drug choice, pretreatment with dopaminergic blocking agents and a comparison of the reinforcing efficacy of cocaine and methylamphetamine. We are particularly interested in correlating measures of mood change and other subjective effects with drugs choice in order to see how they co-vary. Lastly, we are proposing to compile a profile of the cocaine user, look at variables such as drug-taking history and current drug use, and relating these to relevant psycho-social variables.